2-Azaallyl Anions as Light-Tunable Super-Electron-Donors: Coupling with Aryl Fluorides, Chlorides, and Bromides

Title: 2-Azaallyl anions as light-tunable super-electron-donors: coupling

with aryl fluorides, chlorides, and bromides

Authors: Qianmei Wang, Michal Poznik, Minyan Li, Patrick J. Walsh,

and Jason Chruma

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To be cited as: Adv. Synth. Catal. 10.1002/adsc.201800396

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10.1002/adsc.201800396

Advanced Synthesis & Catalysis

FULL PAPER

DOI: 10.1002/adsc.201((will be filled in by the editorial staff))

2-Azaallyl anions as light-tunable super-electron-donors:

coupling with aryl fluorides, chlorides, and bromides

Qianmei Wang^a, Michal Poznik^b*, Minyan Li,^bPatrick J. Walsh,^bJason J. Chruma^a*

a

Key Laboratory of Green Chemistry & Technology, College of Chemistry and Sino-British Materials Research

Institute, College of Physical Science & Technology, Sichuan University, Chengdu, Sichuan 610064, P. R. China, E-

mail: poznik@scu.edu.cn; chruma@scu.edu.cn

Roy and Diana Vagelos Laboratories, Penn/Merck Laboratory for High-Throughput Experimentation, Department of

b

Chemistry, University of Pennsylvania, 231 South 34th Street, Philadelphia, Pennsylvania 19104-6323, United States.

Received: ((will be filled in by the editorial staff))

Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201######.

Abstract. Herein, we present 2-azaallyl anions as colored with visible light can further extend their reducing power,

super-electron-donors capable of reducing a collection of enabling radical-mediated coupling with otherwise

aryl halides via a single electron transfer and coupling with unreactive electron-rich aryl halides. Isolated yields up to

the corresponding radicals to forge new C-C bonds. This 94% are obtained and the overall relevance and utility is

offers a robust approach for the arylation of 2-azaallyls. demonstrated by the derivatization of both a known

Mechanistic studies demonstrate that the reactions proceed pharmaceutical agent and a popular fluorophore.

via either a radical pathway for aryl bromides and chlorides

or a S_NAr mechanism for activated aryl fluorides. Moreover,

we demonstrate that irradiation of the colored 2-azaallyl

anions

Keywords: electron transfer; 2-azaallyl; organic reductants;

photochemistry; visible light

anions,^[7]it was recently discovered that these anionic

species can couple with vinyl bromides under

transition-metal-free conditions (Figure 1a).^[7h]

Computational studies and EPR measurements

suggested the presence of radical species, possibly 2-

azaallyl radicals, in the reaction. The intermediacy of

2-azaallyl radicals was confirmed in later studies

where 2-azaallyl anions acted as SEDs to reduce and

couple with aryl iodides and alkyl iodides/bromides

(Figure 1b).^[8]The resulting diarylmethylamine

derivatives are of importance to the pharmaceutical

industry.^[9].

Introduction

The formation of C–C bonds is arguably one of the

most desired transformations in synthetic organic

chemistry. Very recently, there has been a substantial

thrust to identify unique transition-metal-free

strategies for forging C-C bonds.^[1]One such popular

approach involves utilizing radicals as active

intermediates.^[2]An advantage of this tactic is that it

readily allows for coupling to C(sp³) centers. Several

strategies for generating and recombining C-centered

radicals have been reported, with light-initiated

processes receiving growing attention.^[3]In such

processes, single-electron transfer (SET) to or from

an excited state catalyst is frequently employed to

generate a radical species, which then undergoes

further transformations.^{[3c, 4]}The redox potential of

these photocatalysts is, therefore, one of the key

features regarding their potencies. An alternative

approach for the generation of radical species is to

use organic compounds, termed super-electron-

donors (SEDs), which are capable of directly

performing SET. The redox potentials for known

neutral SEDs can be as low as -1.5 V (vs. SCE).^[5]

Another photochemical approach for reducing aryl

halides to aryl radicals is via visible light irradiation

of electron donor-acceptor (EDA) complexes.^[6]

In this work, we build on the concept of 2-azaallyl

anions as SEDs in the absence of added transition-

metals for their coupling with a collection of

previously

unreactive

electron-deficient

aryl

bromides, chlorides, and fluorides (Figure 1c). Most

significantly, we capitalize on an often overlooked

feature of 2-azaallyl anions, their beautiful deep

reddish-purple color, which opens the door to excited

state reactivity mediated by visible light. Specifically,

we discovered that photoexcitation of 2-azaallyl

anions using green or blue LEDs enhanced their

reactivity sufficiently to perform reductive C–C

couplings with otherwise unreactive electron-rich aryl

bromides and chlorides. Mechanistic investigations

strongly suggest that 2-azaallyl anions are indeed

capable of performing SET with aryl halides to create

transient aryl radicals, which can then react with the

resultant 2-azaallyl radicals.^[10]A slightly different

As part of a larger research program focused on the

generation and functionalization of 2-azaallyl

1

10.1002/adsc.201800396

Advanced Synthesis & Catalysis

radical pathway (S_RN1) cannot be ruled out at this

time for electron-deficient aryl bromides/chlorides.

Activated aryl fluorides, on the other hand, follow the

classic S_NAr mechanism. Overall, these studies make

evident that 2-azaallyl anions are powerful SEDs with

very high and light-tunable redox potentials capable

of reducing most aryl bromides and chlorides to the

corresponding aryl radicals. These results mandate

reconsideration of mechanistic proposals involving 2-

azaallyl intermediates in nucleophilic cross couplings

reported over the past century.^{[7e, 11]}

optimization of the reaction conditions showed that

use of NaH (1.5 equiv) as base and a 3:1 ratio of

ketimine 1a to aryl chloride 2a in the absence of

exogenous light provided the highest isolated yield of

3aa (82%). With these conditions in hand, we tested

the substrate scope with a collection of electron-poor

aryl bromides, chlorides, and fluorides (2a–d, 2b’–c’,

2b”–d”, Figure 2) and obtained yields for the

corresponding arylated products 3 ranging from 34%

to 89%. The optimal base for the coupling reaction

proved to be substrate specific. For example, using

LiN(SiMe₃)₂(2.5 equiv) as base afforded a near

doubling in the resulting yields for aryl chlorides 2d

(34% → 61%) and 2c (46% → 91%), as well as aryl

bromide 2c” (56% → 94%). Importantly, the new

C-C bond formed exclusively at the formerly

halogenated positions on the aromatic substrates

despite the presence of potentially competitive

electrophilic functional groups such as ketones (2a),

aldehydes (2b, 2b’, and 2b”), nitriles (2c, 2c’, and

2c”), and esters (2d, 2d”).

Figure 1. Previous research on 2-azaallyl radicals, their

reactivity, and scope of this work.^[7h-8]

Figure 2. Substrate scope for the arylation of the 2-

azaallyl anion from 1a with electron-poor aryl halides

Results and discussion

in the dark (0.3 mmol ketimine, 0.1 mmol aryl halide,

Non-irradiated reactions

a

1 mL DMSO, 0.15 mmol NaH).

0.25 mmol

LiN(SiMe₃)₂used as a base instead of 0.15 mmol NaH.

Previous attempts to couple 2-azaallyl anions with

various aryl bromides and chlorides required the use

of either a palladium or nickel catalyst to achieve

Irradiated reactions

acceptable yields.^[7f-7j,

Under these reaction

12]

conditions, electron-rich aryl halides tend to out-

perform their electron-deficient counterparts. In

considering a radical pathway for the coupling

without added transition-metals,^[11]however, the

redox potential of the aryl halide is paramount and

As shown in Figure 2, attempts to use these reaction

conditions to couple 1a with the relatively electron-

rich 4-(tert-butyl)bromobenzene 2e’’ failed to afford

product 3ae. Given our previous success in coupling

2-azaallyl anions with aryl iodides, this lack of

reactivity may indicate that the reducing power of the

anion of 1a is not sufficient to undergo SET with aryl

bromide 2e”. Accordingly, increasing the reducing

power of the 2-azaallyl anion SED should allow for

coupling with less reactive aryl halides. Given that

the 2-azaallyl anion generated by deprotonation of 1a

is deeply colored (reddish-purple), we reasoned that

photoexcitation of this anionic intermediate with

visible light should result in a more reactive excited

state species. Indeed when 1a was deprotonated with

should

favor

electron-deficient

substrates.

Accordingly, we focused on p-chloroacetophenone

(2a) as a plausible substrate. Examination of the

palladium-free coupling between the lithiated anion

of 1a and electron-poor aryl chloride 2a in THF

showed no reaction. Since it is known that solvent

polarity can have a drastic effect on the reactivity of

radical reactions,^[13]we screened several solvents and

found that switching to DMSO resulted in the

formation of 3aa (13%, see Supporting Information

for complete optimization studies). Further

2

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Advanced Synthesis & Catalysis

LiN(SiMe₃)₂in the presence of 2e’’ and irradiated

with blue LEDs for 4 h, 18% of the arylated product

3ae was observed (see Supporting Information).

Further optimization of these photo-irradiated

reaction conditions revealed that using ketimine 1a as

the limiting reagent (with up to 10 equiv of the aryl

halide) and n-butyl lithium (n-BuLi, 2 equiv;

deprotonation likely takes place via the anion of

DMSO) as base resulted in both the highest yield and

shortest reaction time (see Supporting Information for

complete optimization studies). If necessary, the

amount of aryl halide can be scaled down to 2 equiv.

resulting in only a 10% decrease in yield (see

Supporting Information, Figure S5). Moreover,

irradiation with lower-energy green LEDs resulted in

similar yields but was preferred for its milder

character. In contrast to the non-irradiated couplings

with activated aryl halides (Figure 2), photo

irradiated coupling between 1a and 4-(tert-

butyl)bromobenzene (2e”) produced a small amount

of the regioisomeric product 4ae in addition to

diarylmethylimine 3ae (3ae:4ae, 4:1, Figure 3).^[10]

These conditions were successfully applied to an

array of aryl bromides (2e’’–k’’) and aryl chlorides

(2f,g,i) to afford the resulting arylated products, as a

mixture of regioisomers (Figure 3). This mixture can

be separated by column chromatography. Combined

yields tended to be modest and decreased as the

electron density of the aryl halides increased. For

example, electron-neutral substrates bromobenzene

(2f”) and chlorobenzene (2f) coupled with the anion

of 1a upon irradiation with green light to afford a 4:1

mixture of 3af and 4af in 58% or 52% combined

yield, respectively.

Coupling with the electron-rich p-haloanisoles 2i”

and 2i, on the other hand, produced a roughly 2:1

mixture of 3ai and 4ai in 32% or 24% combined

yield. 2-Bromoaniline 2j” was unreactive. In all cases,

the aryl bromides afforded higher yields of the

coupled products in comparison to the analogous aryl

chlorides. S-Heterocycle 2-bromothiophene 2l’’

exhibited reactivity (quick discoloration of the

reaction mixture when irradiated), but afforded only

very low amounts of product 3al (4%). Under both

of our reaction conditions (dark or irradiated), neither

bromofurane 2m” nor fluorobenzene 2f’ coupled

with 1a. Nevertheless, access to such a broad

substrate scope of electron-poor aryl halides under

non-irradiated conditions (2a-d, 2b’,c’, 2b”-d”,

Figure 2) and electron-neutral/rich aryl bromides and

chlorides under irradiated conditions (2f,g,i, 2e’’-k’’,

Figure 3) is of great importance and unprecedented

for transition-metal-free radical-mediated C-C cross

couplings.

Different 2-azaallyls

In order to further explore the scope of this method,

we prepared three aldimines, which upon

deprotonation generated similarly colored 2-azaallyls

(Figure 4). We selected these substrates for their

variable electron density, from the electron-donating

methoxy group in 1b to the electron-withdrawing

cyano substituent in 1d. It is possible that electron

density could have an effect on the reducing power of

the 2-azaallyl anion. Moreover, in order to test the

robustness of the method and provide a strategy for

the introduction of heterocycles, the thiophene

derivative 1c was also prepared. So as to focus our

attention on electronic factors, we only examined

1,1,3-tris-arylated 2-azaallyl anions with relatively

similar pK_avalues and steric constraints. Alkyl

aldimines are not appropriate for this strategy as they

preferentially form 1-azaallyl anions (enaminates)

under our reaction conditions.^[14]

1

Ph

0.8

4-MeO-Ph

0.6

0.4

2-Thiophene

4-CN-Ph

0.2

0

450

500

550

600

650

700

Wawelength (nm)

Figure 4. Normalized UV-Vis spectra of 2-azaallyl

anions.

Figure 3. Substrate scope for the transition-metal-free

arylation of the 2-azaallyl anion from 1a with aryl

halides in the presence of green light (0.2 mmol 1a, 2

mmol aryl halide, 2 mL DMSO, 0.4 mmol n-BuLi).^a

In coupling these three aldimines (1b–d), individually,

with 4-chlorobenzonitrile 2c in the absence of light,

we observed very similar reactivity (albeit with lower

isolated yields, 29–65%, Figure 5) to that which we

observed with the 2-azaallyl anion generated from

ketimine 1a (91%). Arylation of these 2-azaallyl

anions with bromobenzene (2f’’) took place only in

b

Determined via ¹H NMR analysis,

Isolated yield

refers to 3ah only; 4ah decomposed during

c

purification, Determined after isolation via column

chromatography, ^dIsolated yield refers to 3al only; 4al

was not isolated.

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Advanced Synthesis & Catalysis

the presence of visible light. This approach proved to

be much better for the preparation of heterocycle-

containing derivatives like 3al. In the case of p-

cyanobenzaldimine 1d, only a trace amount of

product 3df was observed (<7%) under green light

irradiation, but a 2:1 mixture of regioisomers 3df and

4df was obtained in 63% combined yield upon using

blue light. Very similar reactivity was recorded

between the anion of 1d with chlorobenzene (2f´).

The similar reactivity patterns make evident that

slight electronic modifications to the 2-azaallyl anion

framework do not afford significant differences in the

resulting redox potential. The only noticeable

difference is that the electron poor cyano derivative

1d required the use of higher energy blue light to

couple with halobenzenes 2f” and 2f.

Figure 6. Modification of the marketed drug

fenofibrate and chromophore 10 under non-irradiated

conditions.

Mechanistic studies

In our previous studies with electron-neutral/rich aryl

iodides, we proposed that the 2-azaallyl anion

intermediates act as SEDs to perform SET with the

organohalides.^[8]In those studies, we noted that

mixtures of regioisomers, e.g 3 and 4, were formed

unless steric factors, such as substituents ortho to the

iodide leaving group, dictated otherwise. Under the

photo-irradiated reaction conditions for the coupling

of excited-state 2-azaallyls with electron-rich aryl

bromides and chlorides reported herein, we observed

essentially identical regioselectivities (3:4) as

observed for the non-irradiated couplings with the

corresponding aryl iodides. Accordingly, we propose

Figure 5. Isolated yields and regioselectivities for the

arylation of 2-azaallyl anions generated from aldimines

1b-d

.

Application

To explore the overall utility, we first applied the

coupling of 2-azaallyl anions with activated aryl

halides to the modification of fenofibrate, a drug used

to manage high cholesterol levels. All four 2-azaallyl

anions generated from imines 1a–d successfully

coupled with fenofibrate in the absence of light to

afford the modified compounds (5, 6, 7, and 8,

respectively) in moderate to good yields (38%-64%,

Figure 6). Moreover, the benzophenone imine moiety

in derivative 5 was successfully hydrolyzed to obtain

free amine 9 in 85% isolated yield. The method was

also successfully used to modify the important

bromonaphthaleneimide chromophore 10^[15]in high

yield (>80%) at both microgram and a gram scale.

Hydrolysis of the resulting imine 11 proceeded

smoothly to obtain amine 12 (59% yield), allowing

for further derivatization or linkage of the

chromophore to other scaffolds.

a

similar reaction mechanism for these

transformations. Namely, direct coupling between the

aryl radical generated after ejection of the halide and

the relatively persistent 2-azaallyl radical formed in

the initial SET event (Figure 7, top). It should be

emphasized that the observed regioselectivities using

electron neutral/rich aryl halides are dependent on

only the nature of the 2-azaallyl framework and not

the particular halide employed.

The non-irradiated couplings between 2-azaallyls and

electron-deficient aryl halides are unique in that

arylation only occurs at the less substituted carbon of

the 2-azaallyl framework, leading to the exclusive

formation of regioisomer 3. This dramatic difference

in observed regioselectivity may indicate, but does

not necessitate, that the transformations proceed via a

different reaction mechanism (Figure 7, bottom). SET

between the 2-azaallyl anion SED and activated aryl

halide still would form a 2-azaallyl radical and, after

ejection of the halide, an aryl radical. In this

circumstance, however, the electron-withdrawing

group (EWG) on the aromatic ring could stabilize the

aryl radical intermediate. Such increased stability

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10.1002/adsc.201800396

Advanced Synthesis & Catalysis

could lead to better regioselectivity in the direct

coupling with the 2-azaallyl radical. Alternatively, as

depicted in Figure 7 (bottom), the relatively persistent

aryl radical could couple with the more abundant 2-

azaallyl anion species via an S_RN1 pathway.

Reduction of the resultant radical anion either by SET

with another equivalent of aryl halide (shown) or the

2-azaallyl radical (not shown) would afford the

observed product 3. Prior mechanistic studies using

Bunnett and Crearys’ 1,4-dihalobenzenes^{[7, 15]}did not

support a S_RN1 mechanism, but such a pathway

cannot be ruled out at this time for the coupling of 2-

azaallyls with electron-deficient aryl halides.

is S_NAr. To test this possibility, we synthesized two

radical-clock probes, aryl chloride 14 and fluoride 15

(Figure 8c). SET to generate an aryl radical will

result in rapid cyclization with the pendant allyl

moiety prior to any intermolecular couplings. In the

case of chloride 14 with ketimine 1a, use of either

NaH or LiN(SiMe₃)₂as base resulted in a

diastereomeric mixture (dr = 1.1:1, see Supporting

Information) of cyclized products (16) in 68% yield.

This result provides concrete evidence that electron-

poor aryl chlorides (and most likely aryl bromides)

couple with 2-azaallyl anions via

a

radical

mechanism.^[8]Such a result is remarkable and would

not have been predicted prior to our identification of

2-azaallyl anions as SEDs. The reaction between the

fluorinated derivative 15 and the 2-azaallyl anion

derived from 1a afforded the non-cyclized S_NAr

product 17 in 63% yield. This result was not

surprising given the difficulty in reducing unactivated

aryl fluorides,^[16]which also explains the lack of

reactivity for fluorobenzene (2d”, Figure 3).

Compounds 3an and 16 also serve as evidence that

this arylation strategy can be used for more

substituted aryl halides.

Figure 7. Potential mechanisms for the arylation of 2-

azaallyl anions using either electron-rich aryl halides

with visible light (top) or electron-deficient aryl

halides in the dark (bottom).

To further explore the reaction mechanisms, we

performed several experiments. Ketimine 1a

successfully coupled with 2,6-dimethylbromobenzene

(2n) upon irradiation of the reaction mixture with

green light to afford the product 3an in 32% yield,

thus excluding benzyne intermediates (Figure 8a).

Additionally, the coupling between the 2-azaallyl

anions and aryl halides in the light or in the dark

occurred exclusively at the aromatic carbon where the

halogen atom was originally located. In a separate

experiment, we carefully analyzed the coupling

between 1a and 4-tert-butylbromobenzene (2a) by

GC-MS and detected the presence of several

byproducts that most likely arise by radical-radical

coupling (dimer 13) or hydrogen atom transfer (HAT,

tert-butylbenzene, Figure 8b). It should be noted that

dimer 13 was typically the major side product (up to

50% as a 1.5:1 mixture of meso and rac

diastereomers) in all of the coupling reactions

involving ketimine 1a throughout both these and our

previous studies.^[8]Another potential mechanism for

the arylation of 2-azaallyl anions with electron-poor

aryl halides in the absence of added transition-metals

Figure 8. Selection of mechanistic studies that support

a

radical pathway for aryl chlorides and bromides with

and without light.

Redox potential estimates

Given that the first step in the proposed mechanism

for the reaction of the ground state and excited state

5

10.1002/adsc.201800396

Advanced Synthesis & Catalysis

2-azaallyl anions with the aryl halide is SET,

estimation of the redox potentials of these species is

of paramount importance. Our previous efforts to

measure the redox potential of this anion by cyclic

voltammetry failed due to the rapid dimerization of

the 2-azaallyl radical upon formation. A rough

estimate for the reducing power of the 2-azaallyl

anion derived from 1a can be made by comparison

with the known redox potentials of the aryl halide

substrates (Figure 9). The resulting estimated values

are illustrative of the remarkable potentials as single-

electron reducing agents. As seen in Figure 9, there is

a clear difference in reducing ability between the

ground-state anion and its photo-excited counterpart.

Based on reactivity studies, the ground state 2-

azaallyl anion can be estimated at –2.1 V; most aryl

halide substrates with redox potentials below this

value will not couple to the 2-azaallyl anion from 1a

in the dark. It is worth mentioning that the reported

redox potentials of compounds like chlorobenzene (2f,

–2.61 V) and 4-chloroanisole (2i, –2.77 V) are

significant and out-of-reach for a majority of other

reported organic or organometallic photocatalysts,

hence forming radicals from them is a very

challenging task.^[17]Such unprecedented reactivity

demonstrates that the visible light photo-excited

states of 2-azaallyl anions indeed have exceptionally

strong reducing capabilities, with redox potentials

around –2.8 V! As seen for modified 2-azaallyls

prepared from compounds 1b-d, the reactivity is

similar to 1a and none of the compounds require light

to react with 4-chlorocyanobenzonitrile 2c. Moreover,

none of these 2-azaallyl anions can reduce

bromobenzene 2f’’ in the dark. Overall, this shows

that electronic variations in the parent 2-azaallyl

anion framework do not drastically impact the

resulting redox potentials.

remarkable reducing potentials capable of forming

aryl radicals from even electron-rich aryl chlorides

when irradiated with visible light. To the best of our

knowledge, this is the first example of

a

photochemical transformation of 2-azaallyl anions

using visible light. Even in the dark, however, the

radical-mediated coupling between (ground state) 2-

azaallyl anions and electron-poor aryl halides offers a

robust and high-yielding method for the construction

of pharmaceutically-relevant diarylmethylamine

derivatives. We hope that these findings provide not

only

a

valuable synthetic to1bol but, more

importantly, a possible template for designing other

SEDs and organic dyes with high redox potentials.

Investigations in these directions are currently

underway.

Experimental Section

Preparation of ketimine 1a and aldimines 1b–d

N-(Diphenylmethylene)-1-phenylmethanamine (1a)

Prepared by

a

modification of published

procedures.^[19]A flame-dried round-bottom flask

equipped with a stir bar was charged with

benzophenone imine (5.2 mL, 31 mmol),

dichloromethane (12.5 mL), and benzylamine (3.4

mL, 31 mmol) and the resulting reaction mixture was

stirred at 25°C for 16 h. The solvent was evaporated

under reduced pressure. The resulting residue was

then crystalized from EtOAc/hexanes to provide

ketimine 1a as a white solid (6.308 g, 75%). The

NMR spectra matched previously published data.^[20]

N-(4-Methoxybenzylidene)-1,1-diphenylmethanamine (1b)

A flame-dried round-bottom flask equipped with a

stir bar was charged with p-methoxybenzaldehyde

(688 mg, 5 mmol), followed by addition of diphenyl-

methanamine (1 mL, 5.5 mmol) via syringe. The

100

90

80

70

60

50

40

30

20

10

0

o

resulting mixture was then stirred at 65 C for 4 h

under vacuum and the produced solid was

recrystallized from EtOAc/hexanes to afford aldimine

1b as a white solid (1.145 g, 76%). The NMR spectra

matched previously published data.^[21]

DARK

550 nm

1,1-Diphenyl-N-(thiophen-2-ylmethylene)methanamine (1c)

-1.9 -1.94 -1.97 -2.02 -2.08 -2.21 -2.23 -2.5 -2.61 -2.77

Redox potential / V vs SCE

A flame-dried round-bottom flask equipped with a

stir bar was charged with 2-thiophenaldehyde (1 mL,

10.7 mmol), followed by addition of diphenyl-

methanamine (2 mL, 11.8 mmol) via syringe. The

Figure 9. Reducing power of a 2-azaallyl anion (from

1a) in ground (blue) and excited states (red) as

estimated from a correlation of its yields depending on

the redox potentials (vs SCE) of the aryl halide

substrates.^[18]

o

resulting mixture was then stirred at 65 C for 5 h

under vacuum and the produced solid was

recrystallized from EtOAc/hexanes to afford 1c as a

white solid (2.553 g, 86%). The NMR spectra

matched the previously published data.^[22]

Conclusions

4-((Benzhydrylimino)methyl)benzonitrile (1d)

In conclusion, we present a new feature of 2-azaallyl

anions, namely that they are light-tunable SEDs with

6

10.1002/adsc.201800396

Advanced Synthesis & Catalysis

A flame-dried round-bottom flask equipped with a

stir bar was charged with 4-cyanobenzaldehyde

(2.360 g, 18 mmol), followed by addition of

diphenylmethanamine (3.4 mL, 19.8 mmol) via

syringe. The resulting mixture was then stirred at 65

^oC for 4 h under vacuum and the produced solid was

recrystallized from EtOAc/hexane to provide

aldimine 1d as a white solid (4.268 g, 80%). The

NMR spectra matched the previously published

data.^[23]

A flame-dried vial charged with a stir bar and

ketimine/aldimine 1 (0.2 mmol) was left under

reduced pressure for 30 min, then, after refilling the

vial with argon, aryl halide (2 mmol) was introduced.

Dry DMSO (2 mL) then was added under argon via

syringe through the rubber septum. The reaction

mixture was degassed with three consecutive

vacuum/argon-fill cycles, followed by addition of a

solution of n-BuLi (1.6 M, 0.25 mL, 0.4 mmol). The

resulting dark purple/blue solution was irradiated

with green LED light while stirring at room

temperature (20-25 °C). Reaction completion was

determined to occur when the dark color disappeared

and the reaction turned yellow/green. The vial was

then opened to air, poured into a half-saturated

aqueous solution of NH₄Cl (8 mL), extracted with

EtOAc (4 × 2 mL), dried (MgSO₄), filtered, and

concentrated under reduced pressure. The residue was

purified by column chromatography using the

indicated eluent.

General procedures for arylation

Procedure A: Arylation using electron-poor aryl halides (dark

reaction conditions)

A flame-dried vial charged with a stir bar and

ketimine/aldimine 1 (0.3 mmol) was left under

reduced pressure for 30 min, then, after refilling the

vial with argon, aryl halide (0.1 mmol) was

introduced. The vial was then further degassed with

three consecutive vacuum/argon-fill cycles, after

which NaH (6 mg, 60% dispersion in mineral oil,

0.15 mmol) was added in a glove-box. Dry DMSO (1

mL) then was added under argon via syringe through

the rubber septum (the reaction mixture slowly turned

dark purple/blue). The reaction mixture was stirred at

room temperature (20-25 °C) in the dark (covered

with a thick cardboard box). Progress was monitored

by TLC until reaction completion. The vial was then

opened to air, poured into a half-saturated aqueous

solution of NH₄Cl (8 mL), extracted with EtOAc (4 ×

2 mL), dried (MgSO₄), filtered, and concentrated

under reduced pressure. The resulting residue was

purified by column chromatography using the

indicated eluent.

Arylations in dark

1-(4-(((Diphenylmethylene)amino)(phenyl)methyl)phenyl)ethan-

one (3aa)

The reaction was performed following general

procedure A using ketimine 1a (81 mg, 0.3 mmol)

and 4-chloroacetophenone 2a (13 µl, 15 mg, 0.1

mmol) with a reaction time of 6 h. The crude material

was purified by column chromatography (eluent: 1%

Et₃N in 2% EtOAc/petroleum ether) to afford 3aa (32

mg, 82%) as a colorless thick oil. An analytical

sample for characterization was further purified using

normal-phase HPLC (10% 2-propanol/hexane). R_f=

1

0.19 (10% EtOAc/petroleum ether); H NMR (400

MHz, CDCl₃) δ 7.87 (d, J = 8.3 Hz, 2H), 7.78 – 7.70

(m, 2H), 7.48 – 7.16 (m, 13H), 7.08 – 7.01 (m, 2H),

5.59 (s, 1H), 2.54 (s, 3H); ¹³C NMR (101 MHz,

CDCl₃) δ 197.9, 167.7, 150.4, 144.1, 139.6, 136.5,

135.7, 130.4, 128.8, 128.7, 128.6, 128.6, 128.1, 127.7,

127.7, 127.6, 127.1, 69.7, 26.6; IR (thin film): ν_max

3058.6, 1681.4, 1614.3; HRMS (ESI+) m/z 390.1835.

[(M+H)⁺; calculated mass for C₂₈H₂₄NO⁺: 390.1852].

Procedure A’: Arylation using electron-poor aryl halides (dark

reaction conditions)

A flame-dried vial charged with a stir bar and

ketimine/aldimine 1 (0.3 mmol) was left under

reduced pressure for 30 min, then, after refilling the

vial with argon, aryl halide (0.1 mmol) was

introduced. The vial was then further degassed with

three consecutive vacuum/argon-fill cycles. Dry

DMSO (1 mL) was added under argon via syringe

through the rubber septum followed by a solution of

LiN(SiMe₃)₂in THF (0.25 mL, 1M, 0.25 mmol); the

reaction quickly turned dark purple/blue. The reaction

mixture was stirred at room temperature (20-25 °C)

in the dark (covered with a thick cardboard box).

Progress was monitored by TLC until reaction

completion. The vial was then opened to air, poured

into a half-saturated aqueous solution of NH₄Cl (8

mL), extracted with EtOAc (4 × 2 mL), dried

(MgSO₄), filtered, and concentrated under reduced

pressure. The resulting residue was purified by

column chromatography using the indicated eluent.

4-(((Diphenylmethylene)amino)(phenyl)methyl)benzaldehyde

(3ab)

From fluoride: The reaction was performed

following general procedure A using ketimine 1a (81

mg, 0.3 mmol) and 4-fluorobenzaldehyde 2b’ (11 µL,

12 mg, 0.1 mmol) with a reaction time of 10 min. The

crude material was purified by column

chromatography (eluted with 1% Et₃N in 2%

EtOAc/petroleum ether) to give the product 3ab (21

mg, 56%) as a colorless thick oil.

From chloride: The reaction was performed

following general procedure A with ketimine 1a (82

mg, 0.3 mmol) and 4-chlorobenzaldehyde 2b (14 mg,

0.1 mmol) with a reaction time of 10 min. The crude

material was purified by column chromatography

(eluted with 1% Et₃N in 2% EtOAc/petroleum ether)

Procedure B: Arylation using electron-rich aryl halides

(photochemical conditions)

7

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Advanced Synthesis & Catalysis

to give the product 3ab (20 mg, 52%) as a colorless

thick oil.

to give the product 3ac (35 mg, 94%) as a colorless

thick oil.

From bromide: The reaction was performed

following general procedure A with ketimine 1a (82

mg, 0.3 mmol) and 4-bromobenzaldehyde 2b’’ (19

mg, 0.1 mmol) with a reaction time of 6 min. The

crude material was purified by column

chromatography on silica gel (eluted with 1% Et₃N in

2% EtOAc/petroleum ether) to give the product 3ab

(25 mg, 67%) as a colorless thick oil.

In all cases, the NMR spectra matched the previously

published data.^[7f]

Methyl 4-(((diphenylmethylene)amino)(phenyl)methyl)benzoate

(3ad)

From chloride: The reaction was performed

following general procedure A with ketimine 1a (82

mg, 0.3 mmol) and methyl 4-chlorobenzoate 2d (17

mg, 0.1mmol) with a reaction time of 1 h. The crude

material was purified by column chromatography

(eluted with 1% Et₃N in 2% EtOAc/petroleum ether)

to give the product 3ad (14 mg, 34%) as a thick

colorless oil.

The reaction was also performed following general

procedure A’ with ketimine 1a (82 mg, 0.3mmol) and

methyl 4-chlorobenzoate 2d (17 mg, 0.1mmol) with a

reaction time of 4 h. The crude material was purified

by column chromatography (eluted with 1% Et₃N in

2% EtOAc /petroleum ether) to give the product 3ad

(25 mg, 61%) as a thick colorless oil.

An analytical sample for characterization was further

purified using HPLC (1.3% 2-propanol/hexane). R_f=

1

0.41 (10% EtOAc /petroleum ether + 1% Et₃N); H

NMR (400 MHz, CDCl₃) δ 9.96 (s, 1H), 7.85 – 7.70

(m, 4H), 7.55 – 7.17 (m, 13H), 7.09 – 6.99 (m, 2H),

5.61 (s, 1H); ¹³C NMR (101 MHz, CDCl₃) δ 192.1,

167.9, 151.9, 143.9, 139.5, 136.5, 135.1, 130.4, 130.0

128.8, 128.7, 128.6, 128.6, 128.2, 128.1, 127.6, 127.6,

127.1, 69.8; IR (thin film): ν_max2923.8, 1699.4,

1605.9, 1579.1 ; HRMS (ESI+) m/z 376.1681.

[(M+H)⁺; calculated mass for C₂₇H₂₂NO⁺: 376.1696].

4-(((Diphenylmethylene)amino)(phenyl)methyl)benzonitrile (3ac)

From bromide: The reaction was performed

following general procedure A with ketimine 1a (82

mg, 0.3 mmol) and methyl 4-bromobenzoate 2d’’ (22

mg, 0.1 mmol) with a reaction time of 1 h. The crude

material was purified by column chromatography

(eluted with 1% Et₃N in 2% EtOAc /petroleum ether)

to give the product 3ad (26 mg, 64%) as a colorless

thick oil.

From fluoride: The reaction was performed

following general procedure A with ketimine 1a (81

mg, 0.3mmol) and 4-florobenzonitrile 2c’ (12 mg, 0.1

mmol) with a reaction time of 10 min. The crude

material was purified by column chromatography

(eluted with 1% Et₃N in 2% EtOAc/petroleum ether)

to give the product 3ac (33 mg, 89%) as colorless

thick oil.

1

R_f= 0.28 (10% EtOAc/petroleum ether); H NMR

(400 MHz, CDCl₃) δ 7.95 (d, J = 8.4 Hz, 2H), 7.77 –

7.72 (m, 2H), 7.47 – 7.17 (m, 13H), 7.07 – 7.02 (m,

From chloride: The reaction was performed

following general procedure A with ketimine 1a (82

mg, 0.3 mmol), 4-chlorobenonitrile 2c (14 mg, 0.1

mmol) with a reaction time of 7 min. The crude

material was purified by column chromatography

(eluted with 1% Et₃N in 2% EtOAc/petroleum ether)

to give the product 3ac (17 mg, 46%) as a colorless

thick oil.

The reaction was also performed following general

procedure A’ with ketimine 1a (82 mg, 0.3 mmol)

and 4-chlorobenonitrile 2c (14 mg, 0.1 mmol) with a

reaction time of 1 h. The crude material was purified

by column chromatography (eluted with 1% Et₃N in

2% EtOAc/petroleum ether) to give the product 3ac

(34 mg, 91%) as a colorless thick oil.

13

2H), 5.59 (s, 1H), 3.88 (s, 3H); C NMR (101 MHz,

CDCl₃) δ 167.7, 167.1, 150.1, 144.2, 139.6, 136.6,

130.3, 129.8, 128.8, 128.7, 128.6, 128.52, 128.5,

128.1, 127.7, 127.6, 127.5, 127.0, 69.7, 52.0; IR (thin

film): ν_max1721.4, 1608.6; HRMS (ESI+) m/z

+

406.1785. [(M+H)⁺; calculated mass for C₂₈H₂₄NO₂:

406.1802].

Arylations under irradiation

1-(4-(tert-Butyl)phenyl)-N-(diphenylmethylene)-1-phenylmethan-

amine (3ae) + N-Benzylidene-1-(4-(tert-butyl)phenyl)-1,1-di-

phenylmethanamine (4ae)

From bromide: The reaction was performed

following general procedure A with ketimine 1a (82

mg, 0.3 mmol) and 4-bromobenonitrile 2c’’ (18 mg,

0.1 mmol) with a reaction time of 7 min. The crude

material was purified by column chromatography

(eluted with 1% Et₃N in 2% EtOAc/petroleum ether)

to give the product 3ac (21 mg, 56%) as a colorless

thick oil.

The reaction was also performed following general

procedure A’ with ketimine 1a (82 mg, 0.3 mmol), 4-

bromobenzonitrile 2c’’ (18 mg, 0.1 mmol) with a

reaction time of 15 min. The crude material was

purified by column chromatography on silica gel

(eluted with 1% Et₃N in 2% EtOAc/petroleum ether)

The reaction was performed following general

procedure B with ketimine 1a (54 mg, 0.2mmol) and

4-bromo-4-tert-butylbenzene 2e’’ (0.28 mL, 2 mmol)

with a reaction time of 2.5 h. The crude material was

purified by column chromatography on silica gel

(eluted with 1% Et₃N in 2% Et₂O/petroleum ether)

to give the mixture of 3ae and 4ae (4:1, 46 mg, 57%)

as a colorless thick oil. The NMR spectra matched

the previously published data.^[7f-8]

N-(Diphenylmethylene)-1,1-diphenylmethanamine (3af) + N-

Benzylidene-1-phenyl-1,1-diphenylmethanamine (4af)

From chloride: The reaction was performed

following general procedure B with ketimine 1a (54

8

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Advanced Synthesis & Catalysis

mg, 0.2 mmol) and chlorobenzene 2f (0.2 mL, 2

mmol) with a reaction time of 4 h. The crude material

was purified by column chromatography on silica gel

(eluted with 1% Et₃N in 2% Et₂O/petroleum ether) to

give the mixture of 3af and 4af (4:1, 36 mg, 52%) as

a colorless thick oil.

From bromide: The reaction was performed

following general procedure B with ketimine 1a (54

mg, 0.2 mmol) and bromobenzene 2f’’ (0.2 mL, 2

mmol) with a reaction time of 3 h. The crude material

was purified by column chromatography on silica gel

(eluted with 1% Et₃N in 2% Et₂O/petroleum ether) to

give the mixture of 3af and 4af (3:1, 40 mg, 58%) as

a colorless thick oil.

characterization failed due to decomposition and/or

hydrolysis of the compound upon chromatography.

3ah: The NMR spectra matched the previously

published data.^[7f]

N-(Diphenylmethylene)-1-(4-methylphenyl)-1-phenylmethan-

amine (3ai) + N-Benzylidene-1-(4-methoxy-phenyl)-1,1-di-

phenylmethanamine (4ai)

From chloride: The reaction was performed

following general procedure B with ketimine 1a (54

mg, 0.2 mmol) and 4-chloroanisole 2i (0.246 mL, 2

mmol) with a reaction time of 6 h. The crude material

was purified by column chromatography on silica gel

(eluted with 2% Et₂O/petroleum ether) to obtain the

3ai (12 mg, 16%) and 4ai (6 mg, 8%) as a colorless

thick oils.

The NMR spectra matched the previously

published data.^[7f-24]

From bromide: The reaction was performed

following general procedure B with ketimine 1a (54

mg, 0.2 mmol) and 4-bromoanisole 2i’’ (0.251 mL, 2

mmol) with a reaction time of 1 h. The crude material

was purified by column chromatography on silica gel

(eluted with 2% Et₂O/petroleum ether) to obtain the

3ai (17 mg, 21%) and 4ai (7 mg, 11%) as a colorless

thick oils.

N-(Diphenylmethylene)-1-(4-methylphenyl)-1-phenylmethan-

amine (3ag) + N-Benzylidene-1-(4-methyl-phenyl)-1,1-diphen-

ylmethanamine (4ag)

From chloride: The reaction was performed

following general procedure B with ketimine 1a (54

mg, 0.2 mmol) and 4-chlorotoluene 2g (0.236 mL, 2

mmol) with a reaction time of 3.5 h. The crude

material was purified by column chromatography on

silica gel (eluted with 1% Et₃N in 2% Et₂O/petroleum

ether) to give the mixture of 3ag and 4ag (4:1, 32 mg,

44%) as a colorless thick oil.

The NMR spectra matched the previously published

data.^[7f-8]

4-(((Diphenylmethylene)amino)(phenyl)methyl)-N,N-dimethyl-

aniline (3aj)

From bromide: The reaction was performed

following general procedure B with ketimine 1a (54

mg, 0.2mmol) and 4-bromotoluene 2g’’ (0.240 mL, 2

mmol) with a reaction time of 3.5 h. The crude

material was purified by column chromatography on

silica gel (eluted with 1% Et₃N in 2%

Et₂O/petroleum ether) to give the mixture of 3ag

and 4ag (3:1, 38 mg, 53%) as a colorless thick oil.

The reaction was performed following general

procedure B with ketimine 1a (54 mg, 0.2mmol) and

4-bromo-N,N-dimethylaniline 2j’’ (400 mg, 2 mmol)

with a reaction time of 2 h. The crude material was

purified by column chromatography on silica gel

(eluted with 1% Et₃N in 10% Et₂O/petroleum ether)

to obtain 3aj (17 mg, 22%) as a colorless thick oil.

The NMR spectra matched the previously published

data.^[7f]

3ag: The NMR spectra matched the previously

published data.^[7f]

1

4ae: R_f= 0.73 (10% EtOAc/petroleum ether); H

NMR (400 MHz, CDCl₃) δ 7.88 – 7.82 (m, 3H), 7.44

– 7.40 (m, 3H), 7.33 – 7.21 (m, 10H), 7.16 – 7.08 (m,

4H), 2.34 (s, 3H); ¹³C NMR (101 MHz, CDCl₃) δ

159.5, 146.1, 142.7, 136.8, 136.4, 130.7, 129.8, 128.6,

128.6, 128.5, 127.7, 126.7, 78.1, 21.0; IR (thin film):

ν_max2924.4, 1642.1; HRMS (ESI+) m/z 362.1907.

[(M+H)⁺; calculated mass for C₂₇H₂₄N⁺: 362.1903].

N-(Diphenylmethylene)-1-(naphthalen-2-yl)-1-phenylmethan-

amine (3ak) + N-Benzylidene-1-(naphthalen-2-yl)-1,1-diphenyl-

methanamine (4ak)

The reaction was performed following general

procedure B with ketimine 1a (54 mg, 0.2mmol) and

2-bromonaphthalene 2k’’ (414 mg, 2 mmol) with a

reaction time of 0.5 h. The crude material was

purified by column chromatography on silica gel

(eluted with 2% Et₂O/petroleum ether) to give 3ak

(14 mg, 13%) and 4ak (10 mg, 18%) as a colorless

thick oils. The NMR spectra matched the previously

published data.^[8]

N-(Diphenylmethylene)-1-phenyl-1-(pyridin-3-yl)methanamine

(3ah) + N-Benzylidene-1-(pyridin-3-yl)-1,1-diphenylmethan-

amine (4ah)

The reaction was performed following general

procedure B with ketimine 1a (54 mg, 0.2 mmol) and

3-bromopyridine 2h’’ (0.193 mL, 2 mmol) with a

reaction time of 2 h. The crude material was purified

by column chromatography on silica gel (eluted with

10% → 25% Et₂O/petroleum ether) to give the 3ah

(20 mg, 29%) as a colorless thick oil. Product 4ah

was most likely present and isolated in the reaction

mixture with R_f= 0.81 (100% EtOAc), but proper

N-(Diphenylmethylene)-1-phenyl-1-(thiophen-2-yl)methanamine

(3al)

The reaction was performed following general

procedure B with ketimine 1a (54 mg, 0.2mmol) and

2-bromothiophene 2l’’ (0.194 mL, 2 mmol) with a

reaction time of 0.5 h. The crude material was

purified by column chromatography on silica gel

9

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Advanced Synthesis & Catalysis

(eluted with 1% Et₂O/petroleum ether) to obtain 3al

(2.6 mg, 4%) as a colorless thick oil. R_f= 0.5 (5%

EtOAc/petroleum ether); ¹H NMR (400 MHz,

CDCl₃) δ 7.78 – 7.73 (m, 2H), 7.48 – 7.16 (m, 12H),

7.11 (dd, J = 6.4, 3.0 Hz, 2H), 6.90 (dd, J = 5.0, 3.6

Hz, 1H), 6.75 (d, J = 3.4 Hz, 1H), 5.78 (s, 1H); ¹³C

1H), 6.75 (d, J = 3.5 Hz, 1H), 5.81 (s, 1H); ¹³C NMR

(101 MHz, CDCl₃) δ 168.8, 149.4, 147.5, 139.1,

135.9, 132.4, 130.7, 129.0, 128.9, 128.7, 128.2,

128.1, 127.5, 126.6, 125.1, 123.7, 119.0, 110.9,

65.5; IR (thin film): ν_max3064.3, 2923.2, 2356.2,

2227.2, 1614.1; HRMS (ESI+) m/z 379.1247.

NMR (101 MHz, CDCl₃) δ 167.5, 149.1, 144.2, 139.6, [(M+H)⁺; calculated mass for C₂₅H₁₉N₂S⁺:

136.3, 130.3, 128.9, 128.7, 128.5, 128.4, 128.1, 127.8, 379.1263].

127.4, 127.1, 126.4, 124.4, 123.3, 66.0; IR (thin

4,4'-(((Diphenylmethylene)amino)methylene)dibenzonitrile (3dc)

film): ν_max3059.0, 1622.2, 1599.0, 1489.9; HRMS

(E+) m/z 354.1274 [(M+H)⁺; calculated mass for

C₂₄H₂₀NS⁺: 354.1311.

The reaction was performed following general

procedure A’ with aldimine 1d (89 mg, 0.3mmol) and

4-chlorobenonitrile 2c (14 mg, 0.1 mmol) with a

reaction time of 3 h. The crude material was purified

by column chromatography (eluted with 1% Et₃N in

5% → 10% EtOAc/petroleum ether) to give the

product 3dc (12 mg, 29%) as a colorless thick oil. R_f

= 0.15 (10% EtOAc/petroleum ether); ¹H NMR

(400 MHz, CDCl₃) δ 7.75 – 7.69 (m, 2H), 7.59 (d, J =

8.3 Hz, 4H), 7.51 – 7.33 (m, 10H), 7.00 (dd, J = 7.7,

1.5 Hz, 2H), 5.60 (s, 1H); ¹³C NMR (101 MHz,

CDCl₃) δ 169.45, 148.8, 138.9, 136.0, 132.5, 130.9,

129.1, 128.8, 128.8, 128.3, 128.2, 127.3, 118.7,

111.2, 69.0; IR (thin film): ν_max3062.9, 2924.9,

2373.6, 2228.7, 1613.4; HRMS (ESI+) m/z

1-(2,6-Dimethylphenyl)-N-(diphenylmethylene)-1-phenylmethan-

amine (3an)

The reaction was performed following general

procedure B with ketimine 1a (54 mg, 0.2mmol) and

2-bromo-m-xylene 2l (0.266 mL, 2 mmol) with a

reaction time of 4 h. The crude material was purified

by column chromatography on silica gel (eluted with

2% Et₂O/petroleum ether) to obtain 3an (24 mg,

32%) as a colorless thick oil. The NMR spectra

matched the previously published data.^[8]

Arylation of selected aldimines

+

398.1652. [(M+H)⁺; calculated mass for C₂₈H₂₀N₃:

4-(((Diphenylmethylene)amino)(4-methoxyphenyl)methyl)benzo-

nitrile (3bc)

398.1652].

N-(Diphenylmethylene)-1-(4-methylphenyl)-1-phenylmethanam-

ine (3bf) + N-Benzylidene-1-(4-methoxy-phenyl)-1,1-diphen-

ylmethanamine (4bf)

The reaction was performed following general

procedure A’ with aldimine 1b (90 mg, 0.3mmol) and

4-chlorobenzonitrile 2c (14 mg, 0.1 mmol) with a

reaction time of 20 min. The crude material was

purified by column chromatography (eluted with 1%

Et₃N in 2% → 5% EtOAc/petroleum ether) to give

the product 3bc (26 mg, 65%) as a colorless thick oil.

From chloride: The reaction was performed

following general procedure B with aldimine 1b (60

mg, 0.2 mmol), chlorobenzene 2f (0.2 mL, 2 mmol)

with a reaction time of 1 h. The crude material was

purified by a column chromatography (eluted with

1% Et₃N in 3% Et₂O/petroleum ether) to give the

mixture of 3bf and 4bf (4:1, 29 mg, 39%) as a

colorless thick oil.

1

R_f= 0.36 (10% EtOAc/petroleum ether); H NMR

(400 MHz, CDCl₃) δ 7.75 – 7.71 (m, 2H), 7.56 (d, J =

8.3 Hz, 2H), 7.48 – 7.31 (m, 8H), 7.20 – 7.15 (m,

2H), 7.06 – 7.00 (m, 2H),, 6.85 – 6.79 (m, 2H), 5.52

(s, 1H), 3.76 (s, 3H); ¹³C NMR (101 MHz, CDCl₃) δ

167.9, 158.7, 150.6, 139.4, 136.4, 135.9, 132.3,

130.4, 128.8, 128.6, 128.1, 127.6, 119.1, 114.0,

110.4, 68.9, 55.3; IR (thin film): ν_max3061.5,

2225.9, 1610.9, 1505.3; HRMS (E+) m/z 403.1797

[(M+H)⁺; calculated mass for C₂₈H₂₃N₂O⁺:

403.1805.

From bromide: The reaction was performed

following general procedure B with aldimine 1b (60

mg, 0.2 mmol) and bromobenzene 2f’’ (0.2 mL, 2

mmol) with a reaction time of 40 min. The crude

material was purified by a column chromatography

(eluted with 1% Et₃N in 3% Et₂O/petroleum ether) to

obtain the 3bf (30 mg, 39%) and 4bf (14 mg, 18%) as

a colorless thick oils.

4-(((Diphenylmethylene)amino)(thiophen-2-yl)methyl)benzo-

nitrile (3cc)

The NMR spectra matched the previously published

data.^[7f-8-21]

The reaction was performed following general

procedure A with aldimine 1c (83 mg, 0.3mmol) and

4-chlorobenzonitrile 2c (14 mg, 0.1 mmol) with a

reaction time of 1 h. The crude material was purified

by column chromatography (eluted with 1% Et₃N in

2% EtOAc/petroleum ether) to give the product 3cc

(24 mg, 63%) as a thick colorless oil. R_f= 0.3 (10%

EtOAc/petroleum ether); ¹H NMR (400 MHz,

CDCl₃) δ 7.77 – 7.72 (m, 2H), 7.58 (d, J = 8.4 Hz,

2H), 7.52 – 7.31 (m, 8H), 7.22 (dd, J = 5.1, 1.1 Hz,

1H), 7.09 – 7.04 (m, 2H), 6.91 (dd, J = 5.1, 3.6 Hz,

N-(Diphenylmethylene)-1-phenyl-1-(thiophen-2-yl)methanamine

(3al) + N-benzylidene-1,1-diphenyl-1-(thiophen-2-yl)methan-

amine (4cf)

From chloride: The reaction was performed

following general procedure B with aldimine 1c (56

mg, 0.2 mmol) and chlorobenzene 2f (0.2 mL, 2

mmol) with a reaction time of 3 h. The crude material

was purified by column chromatography (eluted with

1% Et₃N in 2% Et₂O/petroleum ether) to give the

mixture of 3al and 4cf (2:1, 19 mg, 27%) as a

10

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Advanced Synthesis & Catalysis

Isopropyl 2-(4-(4-(((diphenylmethylene)amino)(phenyl)methyl)-

benzoyl)phenoxy)-2-methylpropanoate (5)

colorless thick oil. Sample of 4cf for characterization

was isolated using HPLC (50% 2-propanol/hexane).

From bromide:

The reaction was performed

The reaction was performed following general

procedure A’ with ketimine 1a (82 mg, 0.3 mmol)

and fenofibrate (36 mg, 0.1 mmol) with a reaction

time of 30 min. The crude material was purified by a

column chromatography (eluted with 1% Et₃N in 5%

EtOAc/petro-leum ether) to give the product 5 (34

mg, 57%) as a colorless oil. R_f= 0.22 (10%

EtOAc/petroleum ether); ¹H NMR (400 MHz,

CDCl₃) δ 7.79 – 7.72 (m, 4H), 7.67 (d, J = 8.3 Hz,

2H), 7.48 – 7.18 (m, 13H), 7.10 – 7.04 (m, 2H), 6.86

– 6.81 (m, 2H), 5.61 (s, 1H), 5.07 (hept, J = 6.3 Hz,

1H), 1.65 (d, J = 5.6 Hz, 6H), 1.19 (d, J = 6.3 Hz,

6H); ¹³C NMR (101 MHz, CDCl₃) δ 195.3, 173.2,

167.6, 159.5, 149.2, 144.2, 139.7, 136.6, 132.0, 130.8,

130.3, 130.0, 128.8, 128.7, 128.5, 128.5, 128.3, 128.1,

127.7, 127.6, 127.4, 127.0, 117.1, 79.4, 69.7, 69.3,

25.4, 21.5; IR (thin film): ν_max2981.7, 1729.3, 1653.6,

1598.6; HRMS (ESI+) m/z 596.2799 [(M+H)⁺;

following general procedure B with aldimine 1c (56

mg, 0.2 mmol) and bromobenzene 2f’’ (0.210 mL, 2

mmol) with a reaction time of 2 h. The crude

material was purified by column chromatography

(eluted with 1% Et₃N in 2% Et₂O/petroleum ether) to

give the mixture of 3al and 4cf (3:1, 26.7 mg, 38%)

as a colorless thick oil. Sample of 4cf for

characterization was isolated using HPLC (50% 2-

propanol/hexane).

4cf: Thick colorless oil. R_f

=

0.56(5%

EtOAc/petroleum ether); ¹H NMR (400 MHz,

CDCl₃) δ 7.86 (s, 1H), 7.43 (dt, J = 5.0, 1.0 Hz, 1H),

7.33 – 7.22 (m, 15H), 7.20 (dd, J = 3.6, 1.0 Hz, 1H),

7.06 (dd, J = 5.0, 3.6 Hz, 1H); ¹³C NMR (101 MHz,

CDCl₃) δ 152.8, 145.7, 143.9, 130.7, 129.7, 129.2,

127.8, 127.4, 126.8, 78.0; IR (thin film): ν_max3059.6,

2923.2, 1629.7, 1489.0; HRMS (E+) m/z 354.1314

[(M+H)⁺; calculated mass for C₂₄H₂₀NS⁺: 354.1311].

+

calculated mass for C₄₀H₃₈NO₄: 596.2795].

4-(((Diphenylmethylene)amino)(phenyl)methyl)benzonitrile (3df)

Isopropyl 2-(4-(4-(((diphenylmethylene)amino)(4-methoxy-

+ 4-((tritylimino)methyl)benzonitrile (4df)

phenyl)-methyl)benzoyl)phenoxy)-2-methylpropanoate (6)

From chloride: The reaction was performed

following general procedure B with aldimine 1d (59

mg, 0.2 mmol) and chlorobenzene 2f (0.200 mL, 2

mmol), reaction irradiated with blue LED for 3 h. The

crude material was purified by column

chromatography (eluted with 1% Et₃N in 5%

Et₂O/petroleum ether) to give the mixture of 3df and

4df (2:1, 31 mg, 42%) as a colorless thick oil.

From bromide: The reaction was performed

following general procedure B with aldimine 1d (59

mg, 0.2 mmol) and bromobenzene 2f’’ (0.200 mL, 2

mmol), reaction irradiated with blue LED for 4.5 h.

The crude material was purified by column

chromatography (eluted with 1% Et₃N in 5%

Et₂O/petroleum ether) to give the mixture of 3df and

4df (2:1, 48 mg, 63%) as a colorless thick oil. Sample

of 4df for characterization was isolated using HPLC

(1.1% 2-propanol/hexane).

The reaction was performed following general

procedure A with aldimine 1b (91 mg, 0.3 mmol) and

fenofibrate (36 mg, 0.1 mmol) with a reaction time of

20 min. The crude material was purified by column

chromatography (eluted with 1% Et₃N in 5%

EtOAc/petro-leum ether) to give the product 6 (36

mg, 57%) as a thick colorless oil. R_f= 0.48 (20%

EtOAc/petroleum ether); ¹H NMR (400 MHz,

CDCl₃) δ 7.80 – 7.72 (m, 4H), 7.67 (d, J = 8.2 Hz,

2H), 7.49 – 7.28 (m, 8H), 7.27 – 7.21 (m, 2H), 7.11 –

7.0 (m, 2H), 6.84 (d, J = 8.8 Hz, 4H), 5.57 (s, 1H),

5.13 – 5.02 (m, 1H), 3.78 (s, 3H), 1.65 (s, 6H), 1.19

(d, J = 6.3 Hz, 6H); ¹³C NMR (101 MHz, CDCl₃) δ

195.3, 173.2, 167.3, 159.5, 158.6, 149.5, 139.7, 136.6,

136.5, 136.5, 132.0, 130.8, 130.2, 130.0, 128.8, 128.7,

128.7, 128.1, 127.7, 127.2, 117.1, 113.9, 79.4, 69.3,

69.1, 55.3, 25.4, 21.5; IR (thin film): ν_max2927.1,

1732.0, 1653.0, 1601.6; HRMS (E+) m/z 626.2912

The reaction was also performed following general

procedure B with aldimine 1d (59.3 mg, 0.2mmol),

bromobenzene 2f’’ (0.200 mL, 2 mmol), reaction

irradiated with green LED for 5 h to give the minute

amount of product 3df (less than 7%, estimated from

+

[(M+H)⁺; calculated mass for C₄₁H₄₀NO₅: 626.2901].

Isopropyl 2-(4-(4-(((diphenylmethylene)amino)(thiophen-2-yl)-

methyl)benzoyl)phenoxy)-2-methylpropanoate (7)

1

crude H NMR using 1,4-dimethoxybenzene as an

The reaction was performed following general

procedure A with aldimine 1c (83 mg, 0.3mmol) and

fenofibrate (36 mg, 0.1 mmol) with a reaction time of

20 min .The crude material was purified by a column

chromatography (eluted with 1% Et₃N in 5%

EtOAc/petroleum ether) to give the product 7 (39 mg,

64%) as a thick colorless oil. R_f= 0.56 (20%

EtOAc/petroleum ether); ¹H NMR (400 MHz,

CDCl₃) δ 7.80 – 7.72 (m, 4H), 7.69 (d, J = 8.3 Hz,

2H), 7.51 – 7.43 (m, 5H), 7.42 – 7.33 (m, 3H), 7.22

(dd, J = 5.1, 1.2 Hz, 1H), 7.13 – 7.08 (m, 2H), 6.93

(dd, J = 5.1, 3.5 Hz, 1H), 6.87 – 6.82 (m, 2H), 6.80 –

6.77 (m, 1H), 5.85 (s, 1H), 5.09 (hept, J = 6.3 Hz,

1H), 1.65 (s, 6H), 1.19 (d, J = 6.3 Hz, 6H); ¹³C NMR

internal standard).

3df: The NMR spectra matched the previously

published data.^[7f]

1

4df: R_f= 0.36 (10% EtOAc/petroleum ether); H

NMR (400 MHz, CDCl₃) δ 7.95 (d, J = 8.4 Hz, 2H),

7.85 (s, 1H), 7.72 (d, J = 8.3 Hz, 2H), 7.35 – 7.21 (m,

15H); ¹³C NMR (101 MHz, CDCl₃) δ 157.9, 145.2,

140.4, 132.4, 129.7, 129.0, 127.9, 127.1, 118.6, 114.0,

78.8; IR (thin film): ν_max2925.1, 2230.8, 1633.9,

1484.3, 1447.7 ;HRMS (ESI+) m/z 373.1755.

+

[(M+H)⁺; calculated mass for C₂₇H₂₁N₂: 373.1699].

Other derivatives

11

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Advanced Synthesis & Catalysis

6-(((Diphenylmethylene)amino)(phenyl)methyl)-2-phenyl-1H-

phenalene-1,3(2H)-dione (11)

(101 MHz, CDCl₃) δ 195.2, 173.2, 168.2, 159.5,

148.3, 148.3, 139.4, 136.9, 136.1, 132.0, 130.7,

130.5, 130.1, 128.9, 128.8, 128.6, 128.1, 127.7,

127.2, 126.6, 124.7, 123.5, 117.2, 79.4, 69.3, 65.8,

25.4, 21.5; IR (thin film): ν_max2983.9, 2934.9, 1730.5,

1653.7, 1601.3; HRMS (ESI+) m/z 602.2349

[(M+H)⁺; calculated mass for C₃₈H₃₆NO₄S⁺:

602.2360].

The reaction was performed following general

procedure A with ketimine 1a (82 mg, 0.3 mmol) and

6-bromo-2-phenyl-1H-benzo[de]isoquinoline-

1,3(2H)-dione (10, 35 mg, 0.1 mmol) with a reaction

time of 15 min. The crude material was purified by a

column chromatography (eluted with 10%

EtOAc/petroleum ether + 1% Et₃N) to give the

product 11 (48 mg, 88%) as a thick oil which

solidified on a pump.

Isopropyl 2-(4-(4-((4-cyanophenyl)((diphenylmethylene)amino)-

methyl)benzoyl)phenoxy)-2-methylpropanoate (8)

The reaction was performed following general

procedure A with aldimine 1d (89 mg, 0.3 mmol) and

fenofibrate (36 mg, 0.1 mmol) with a reaction time of

6 h. The crude material was purified by a column

chromatography (eluted with 1% Et₃N in 5% → 10%

EtOAc/petroleum ether) to give the product 8 (24 mg,

38%) as a thick colorless oil. R_f= 0.54 (20%

EtOAc/petroleum ether); ¹H NMR (400 MHz, CDCl₃)

δ 7.77 – 7.72 (m, 4H), 7.69 (d, J = 8.2 Hz, 2H), 7.60

(d, J = 8.3 Hz, 2H), 7.50 – 7.46 (m, 5H), 7.41 – 7.36

(m, 5H), 7.04 (dd, J = 7.5, 1.7 Hz, 2H), 6.84 (d, J =

8.8 Hz, 2H), 5.63 (s, 1H), 5.08 (hept, J = 6.3 Hz, 1H),

1.65 (s, 6H), 1.19 (d, J = 6.3 Hz, 6H); ¹³C NMR (101

MHz, CDCl₃) δ 195.1 173.2, 168.9, 159.6, 149.5,

147.6, 139.2, 137.1, 136.2, 132.4, 132.0, 130.7,

130.5, 130.2, 129.0, 128.8, 128.7, 128.3, 128.2,

127.5, 127.3, 118.9, 117.1, 110.9, 79.4, 69.3, 69.3,

Gram sacle: The reaction was performed following

general procedure A with ketimine 1a (3.257 g, 12

mmol),

6-bromo-2-phenyl-1H-

benzo[de]isoquinoline-1,3(2H)-dione (10, 1.404 g, 4

mmol) with a reaction time of 30 min. The crude

material was purified by a column chromatography

(eluted with 1% Et₃N in 10% EtOAc /petroleum

ether) to give the product 11 (1.799 g, 83%) as a thick

oil which solidified under vacuum: mp 138 – 140 °C,

1

R_f= 0.32 (15% EtOAc/petroleum ether); H NMR

(400 MHz, CDCl₃) δ 8.66 – 8.61 (m, 1H), 8.57 (dd, J

= 7.3, 1.0 Hz, 1H), 8.44 (dd, J = 8.6, 0.9 Hz, 1H),

8.00 (d, J = 7.7 Hz, 1H), 7.79 – 7.71 (m, 2H), 7.63 –

7.17 (m, 17H), 7.07 (d, J = 6.7 Hz, 2H), 6.34 (s, 1H);

¹³C NMR (101 MHz, CDCl₃) δ 168.7, 164.5, 164.3,

147.9, 143.3, 139.3, 136.3, 135.5, 132.0, 131.6, 131.2,

130.6, 129.6, 129.5, 129.4, 129.0, 128.9, 128.8, 128.7,

25.4, 21.5; IR (thin film): ν_max2985.0, 2930.6, 2226.9, 128.2, 127.6, 127.4, 127.2, 127.2, 126.5, 123.2, 122.0,

1733.9, 1654.2, 1604.9; HRMS (E+) m/z

67.6; IR (thin film): ν_max1712.2, 1667.6,

+

621.2765[(M+H)⁺; calculated mass for C₄₁H₃₇N₂O₄:

1591.9 ;HRMS (ESI+) m/z 543.2070 [(M+H)⁺;

+

621.2748.

calculated mass for C₃₈H₂₇N₂O₂: 543.2067].

Isopropyl 2-(4-(4-(amino(phenyl)methyl)benzoyl)phenoxy)-2-

6-(Amino(phenyl)methyl)-2-phenyl-1H-phenalene-1,3(2H)-dione

methyl-propanoate (9)

(12)

A vial equipped with a stir bar was charged with

compound 5 (34 mg, 0.06 mmol), which was

dissolved in THF (0.6 mL). Then aq. citric acid (1M,

0.6 mL, 0.6 mmol) was added at once. The reaction

mixture was stirred at room temperature for 6 h and

progress monitored by TLC. Upon completion the

reaction mixture was made basic with sat. NaHCO₃

and the mixture was extracted with EtOAc (4 × 2

mL). The combined organic layers were dried

(MgSO₄), filtered, and concentrated under reduced

pressure. The crude material was purified by a

A vial equipped with a stir bar was charged with

compound 11 (55 mg, 0.1 mmol). THF (1 mL) was

o

added and the reaction was cooled at 0 C. Then aq.

HCl (1M, 1 mL) was added to the reaction and during

stirring solution was warmed to room temperature

and progress was monitored by TLC until complete

consumption of 11 (reaction completed in 1 h). The

reaction mixture was made basic with 1M NaOH

until the pH reached 14, then the solution was

extracted with EtOAc (5 × 2mL). The combined

organic layers were dried (MgSO₄), filtered, and

concentrated under reduced pressure. The crude

material was purified by column chromatography on

silica gel (eluted with 1% Et₃N/EtOAc) to give the

amine 12 (23 mg, 59%) as a yellow solid: mp 235 –

column

chromatography

(eluted

with

1%

Et₃N/EtOAc) to give the product 9 (21 mg, 85%) as a

1

thick colorless oil. R_f= 0.27 (100% EtOAc); H

NMR (400 MHz, CDCl₃) δ 7.77 – 7.68 (m, 4H), 7.49

(d, J = 8.1 Hz, 2H), 7.41 – 7.30 (m, 4H), 7.28 – 7.22

1

237 °C, R_f= 0.26 (100% EtOAc); H NMR (400

(m, 1H), 6.87 – 6.82 (m, 2H), 5.28 (s, 1H), 5.08 (hept, MHz, CDCl₃) δ 8.67 (d, J = 7.6 Hz, 1H), 8.59 (d, J =

J = 6.3 Hz, 1H), 1.65 (s, 6H), 1.20 (d, J = 6.3 Hz,

6.7 Hz, 1H), 8.48 (d, J = 8.2 Hz, 1H), 8.13 (d, J = 7.7

Hz, 1H), 7.72 – 7.65 (m, 1H), 7.57 – 7.43 (m, 3H),

6H); ¹³C NMR (101 MHz, CDCl₃) δ 195.2, 173.2,

159.5, 149.7, 145.0, 136.8, 132.0, 130.7, 130.1, 128.7, 7.39 – 7.23 (m, 7H), 6.05 (s, 1H), 2.03 (s, 2H); ¹³C

127.3, 126.9, 126.7, 117.2, 79.4, 69.3, 59.7, 25.4,

NMR (101 MHz, CDCl₃) δ 164.4, 164.2, 148.5, 144.2,

135.4, 131.6, 131.2, 130.6, 129.6, 129.4, 129.1, 129.0,

128.7, 128.7, 127.7, 127.2, 126.9, 125.2, 123.4, 122.0,

21.5; IR (thin film): ν_max2980.0, 2929.9, 1729.3,

1652.1, 1598.9; HRMS (ESI+) m/z 432.2170

+

[(M+H)⁺; calculated mass for C₂₇H₃₀NO₄: 432.2169]. 56.5; IR (thin film): ν_max1707.6, 1665.1, 1589.8;

HRMS (ESI+) m/z 379.1429 [(M+H)⁺; calculated

+

mass for C₂₅H₁₉N₂O₂: 378.1441].

12

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Advanced Synthesis & Catalysis

3-(Allylamino)-4-chlorobenzonitrile

100 °C; the resulting reaction mixture was stirred for

6 h. After cooling to room temperature, the reaction

mixture was poured into water (30 mL) and extracted

with EtOAc (3 × 5 mL). The combined organic layers

were dried (MgSO₄), filtered, and concentrated under

reduced pressure. The crude material was purified by

column chromatography on silica gel (eluted with 1%

Et₃N in 10% Et₂O/petroleum ether) to give the

product (238 mg, 42%) as a colorless oil. R_f= 0.33

In a dried flask under Ar were dispersed 3-amino-4-

chlorobenzonitrile (740 mg, 4.85 mmol) and

potassium carbonate (6692 mg, 48.5 mmol) in dry

DMF (15 mL) at room temperature. Under stirring,

allyl bromide (588 mg, 4.85 mmol, 0.421 mL) was

added dropwise and the temperature was increased to

100 °C; the reaction mixture was stirred for 6 h. After

cooling to room temperature, the reaction mixture

was poured into water (50 mL) and extracted with

EtOAc (3 × 10 mL). The combined organic layers

were dried (MgSO₄), filtered, and concentrated under

reduced pressure. The crude material was purified by

column chromatography on silica gel (eluted with

20% EtOAc/petroleum ether) to give the product (367

mg, 39%) as a colorless oil. R_f= 0.13 (8%

1

(10% EtOAc/petroleum ether); H NMR (400 MHz,

CDCl₃) δ 7.02 (dd, J = 11.1, 8.3 Hz, 1H), 6.97 – 6.91

(m, 1H), 6.88 (dd, J = 8.0, 1.9 Hz, 1H), 5.98 – 5.85

(m, 1H), 5.35 – 5.20 (m, 2H), 4.33 (s, 1H), 3.85 –

3.78 (m, 2H); ¹³C NMR (101 MHz, CDCl₃) δ 153.5

(d, J = 248.3 Hz), 137.3 (d, J = 12.4 Hz), 133.6 (s),

121.2 (d, J = 8.0 Hz), 119.0 (s), 117.1 (s), 115.2 (d, J

= 20.3 Hz), 1155.0 (d, J = 5.1 Hz), 108.7 (d, J = 3.7

Hz), 45.6 (s); IR (thin film): ν_max3417.9, 2229.1,

1612.2, 1522.5; HRMS (ESI-) m/z 175.0703. [(M-

1

EtOAc/hexane); H NMR (400 MHz, CDCl₃) δ 7.33

(d, J = 8.1 Hz, 1H), 6.91 (dd, J = 8.1, 1.8 Hz, 1H),

6.82 (d, J = 1.8 Hz, 1H), 5.98 – 5.86 (m, 1H), 5.34 –

-

H)⁻; calculated mass for C₁₀H₈FN₂: 175.0677].

13

5.21 (m, 2H), 4.71 (bs, 1H), 3.89 – 3.83 (m, 2H); C

NMR (101 MHz, CDCl₃) δ 144.2, 133.4, 129.8, 123.7, 3-(Allyl(methyl)amino)-4-fluorobenzonitrile (15)

120.6, 118.9, 117.2, 113.9, 111.5, 45.7; IR (thin

film): ν_max3414.0, 2231.2, 1590.3, 1511.6; HRMS

In a dried flask under Ar was dissolved 3-

(ESI-) m/z 191.0390 [(M-H)⁻; calculated mass for

(allylamino)-4-fluorobenzonitrile (186 mg, 1.056

mmol) in dry THF (10 mL) and the solution was

cooled to 0 °C. Under stirring, n-BuLi (0.50 mL,

2.5M in hexanes, 1.267 mmol) was added dropwise

followed by dropwise addition of methyl iodide (0.10

mL, 1.584 mmol). The reaction mixture was allowed

to warm to room temperature and stirred for

additional 4 h. The reaction was quenched with sat.

aq. NaHCO₃(10 mL) and extracted with EtOAc (3 ×

10 mL). The combined organic layers were washed

with brine, dried (MgSO₄) filtered, and concentrated

under reduced pressure. The crude material was

purified by column chromatography on silica gel

(eluted with 1% Et₃N in 10% Et₂O/petroleum ether)

to give the product 15 (167 mg, 83%) as a colorless

-

C₁₀H₈ClN₂: 191.0381].

3-(Allyl(methyl)amino)-4-chlorobenzonitrile (14)

In a dried flask under Ar was dissolved 3-

(allylamino)-4-chlorobenzonitrile (285 mg, 1.48

mmol) in dry THF (15 mL) and the solution was

cooled to 0 °C. Under stirring, n-BuLi (1.110 mL, 1.6

M in hexanes, 1.78 mmol) was added dropwise

followed by dropwise addition of methyl iodide (0.12

mL, 1.92 mmol). The reaction mixture allowed to

warm to room temperature and stirred for additional 5

h. The reaction was quenched with sat. aq. NaHCO₃

(10 mL) and extracted with EtOAc (3 × 10 mL). The

combined organic layers were washed with brine,

dried (MgSO₄), filtered, and concentrated under

reduced pressure. The crude material was purified by

column chromatography on silica gel (eluted with 1%

Et₃N in 5% EtOAc/petroleum ether) to give the

product 14 (295 mg, 96%) as a colorless oil. R_f=

1

oil. R_f= 0.44 (10% EtOAc/petroleum ether); H

NMR (400 MHz, CDCl₃) δ 7.16 – 7.00 (m, 3H), 5.92

– 5.77 (m, 1H), 5.26 – 5.16 (m, 2H), 3.79 (d, J = 5.9

Hz, 2H), 2.86 (d, J = 0.7 Hz, 3H); ¹³C NMR (101

MHz, CDCl₃) δ 156.72 (d, J = 254.1 Hz), 140.47 (d, J

= 9.2 Hz), 133.43 (s), 124.37 (d, J = 8.9 Hz), 121.85

(d, J = 5.4 Hz), 118.79 (s), 117.86 (s), 117.29 (d, J =

23.2 Hz), 108.51 (d, J = 3.6 Hz), 57.34 (d, J = 6.3

Hz), 38.92 (d, J = 2.7 Hz); IR (thin film): ν_max2228.9,

1600.6, 1508.1, ; HRMS (ESI+) m/z 191.0987.

1

0.56 (10% EtOAc/petrol-eum ether); H NMR (400

MHz, CDCl₃) δ 7.43 (d, J = 8.1 Hz, 1H), 7.26 (d, J =

1.9 Hz, 1H), 7.19 (dd, J = 8.1, 1.9 Hz, 1H), 5.94 –

5.82 (m, 1H), 5.31 – 5.20 (m, 2H), 3.67 (d, J = 6.1 Hz,

2H), 2.78 (s, 3H); ¹³C NMR (101 MHz, CDCl₃) δ

150.4, 133.9 133.3, 131.7, 125.9, 124.2, 118.4, 111.2,

58.3, 39.5; IR (thin film): ν_max2231.5, 1585.8; HRMS

(ESI+) m/z 207.0659 [(M+H)⁺; calculated mass for

+

[(M+H)⁺; calculated mass for C₁₁H₁₂FN₂: 191.0979].

3-(((Diphenylmethylene)amino)(phenyl)methyl)-1-methylindol-

ine-6-carbonitrile (16)

+

C₁₁H₁₂ClN₂: 207.0684].

The reaction was performed following general

procedure A’ using ketimine 1a (109.3 mg, 0.4

mmol), 3-(allyl(methyl)amino)-4-chlorobenzonitrile

(28 mg, 0.13 mmol) and NaN(SiMe₃)₂(0.4 mL, 1M,

0.4 mmol) with a reaction time of 1 h. The crude

material was purified by column chromatography on

silica gel (eluted with 1% Et₃N in 5% EtOAc/petrol-

eum ether) to give the product 16 as a mixture of

diastereomers (1.1:1, 39 mg, 68%) in the form of

3-(Allylamino)-4-fluorobenzonitrile

In a dried flask under Ar was dispersed 3-amino-4-

fluorobenzonitrile (435 mg, 3.195 mmol) and

potassium carbonate (2.207 g, 15.975 mmol) in dry

DMF (5 mL) at room temperature. Under stirring,

allyl bromide (425 mg, 3.519 mmol, 0.304 mL) was

added dropwise and the temperature was increased to

13

10.1002/adsc.201800396

Advanced Synthesis & Catalysis

thick colorless oil. R_f= 0.29 (10% EtOAc/petroleum

ether). HRMS (ESI+) m/z 442.2269. [(M+H)⁺;

3731-3746; c) H. S. Farwaha, G. Bucher, J. A. Murphy,

Org. Biomol. Chem. 2013, 11, 8073-8081; d) J. Broggi,

T. Terme, P. Vanelle, Angew. Chem. Int. Ed. 2014, 53,

384-413; e) B. Eberle, E. Kaifer, H.-J. Himmel, Angew.

Chem. Int. Ed. 2017, 56, 3360-3363.

+

calculated mass for C₃₁H₂₈N₃: 442.2278].

Diastereomeric ratio was determined based on

indoline methyl group (3H, ~ 2.7 ppm) and aliphatic

1

H (1H, ~ 2.0 ppm), see H spectra for determination

[6] a) B. Liu, C.-H. Lim, G. M. Miyake, J. Am. Chem. Soc.

2017, 139, 13616-13619; b) C. G. S. Lima, T. de M.

Lima, M. Duarte, I. D. Jurberg, M. W. Paixão, ACS

Catalysis 2016, 6, 1389-1407; c) M. A. Fox, J.

Younathan, G. E. Fryxell, J. Org. Chem. 1983, 48,

3109-3112; d) S. Hoz, J. F. Bunnett, J. Am. Chem. Soc.

1977, 99, 4690-4699.

of diastereomeric ratio.

3-(Allyl(methyl)amino)-4-(((diphenylmethylene)amino)(phenyl)-

methyl)benzonitrile (17)

The reaction was also performed following general

procedure A’ with ketimine 1a (92 mg, 0.33 mmol),

3-(allyl(methyl)amino)-4-fluorobenzonitrile (22 mg,

0.11 mmol) and LiN(SiMe₃)₂(0.283 mL, 1M, 0.283

mmol) with a reaction time of 12 h. The crude

material was purified by column chromatography

(eluted with 1% Et₃N in 10% Et₂O/petroleum ether)

to give the product 17 (28 mg, 63%) as a white solid:

mp 150 – 153 °C, R_f= 0.44 (10% EtOAc/petroleum

ether); ¹H NMR (400 MHz, CDCl₃) δ 8.11 (d, J = 8.1

Hz, 1H), 7.74 – 7.65 (m, 2H), 7.48 – 7.13 (m, 13H),

7.07 – 6.98 (m, 2H), 6.17 (s, 1H), 5.30 – 5.17 (m, 1H),

4.99 – 4.89 (m, 2H), 3.06 (d, J = 6.2 Hz, 2H), 2.25 (s,

3H); ¹³C NMR (101 MHz, CDCl₃) δ 167.4, 151.7,

146.5, 144.0, 139.6, 136.9, 134.6, 130.6, 130.2, 128.8,

128.6, 128.4, 128.3, 128.1, 128.0, 127.8, 127.7, 126.8,

125.8, 119.1, 117.6, 110.9, 64.0, 60.5, 41.3; IR (thin

film): ν_max2919.9, 2850.2, 2226.9, 1489.6 ;HRMS

(E+) m/z 442.2270 [(M+H)⁺; calculated mass for

[7] a) A. A. Yeagley, J. J. Chruma, Org. Lett. 2007, 9,

2879-2882; b) W. H. Fields, A. K. Khan, M. Sabat, J. J.

Chruma, Org. Lett. 2008, 10, 5131-5134; c) X. Qian, P.

Ji, C. He, J.-O. Zirimwabagabo, M. M. Archibald, A. A.

Yeagley, J. J. Chruma, Org. Lett. 2014, 16, 5228-5231;

d) W. H. Fields, J. J. Chruma, Org. Lett. 2010, 12,

316-319; e) S. Tang, J. Y. Park, A. A. Yeagley, M.

Sabat, J. J. Chruma, Org. Lett. 2015, 17, 2042-2045; f)

M. Li, B. Yucel, J. Adrio, A. Bellomo, P. J. Walsh,

Chem. Sci. 2014, 5, 2383-2391; g) X. Cao, S.-C. Sha,

M. Li, B.-S. Kim, C. Morgan, R. Huang, X. Yang, P. J.

Walsh, Chem. Sci. 2016, 7, 611-618; h) M. Li, O.

Gutierrez, S. Berritt, A. Pascual-Escudero, A.

Yeşilçimen, X. Yang, J. Adrio, G. Huang, E.

Nakamaru-Ogiso, M. C. Kozlowski, P. J. Walsh, Nat

Chem 2017, 9, 997-1004; i) M. Li, M. González-

Esguevillas, S. Berritt, X. Yang, A. Bellomo, P. J.

Walsh, Angew. Chem. Int. Ed. 2016, 55, 2825-2829; j)

M. Li, S. Berritt, P. J. Walsh, Org. Lett. 2014, 16,

4312-4315.

+

C₃₁H₂₈N₃: 442.2278].

Acknowledgements

[8] M. Li, S. Berritt, L. Matuszewski, G. Deng, A. Pascual-

Escudero, G. B. Panetti, M. Poznik, X. Yang, J. J.

Chruma, P. J. Walsh, J. Am. Chem. Soc. 2017, 139,

16327-16333.

J.J.C. thanks the National Natural Science Foundation

of China (NSFC-21372159) and P.J.W. thanks the

National Science Foundation (CHE-1464744) for

financial support. M.P. and J.J.C. kindly appreciate

Profs. Da-Gang Yu and Cheng Yang (Sichuan

University) for use of their GC-MS and preparatory

HPLC equipment, respectively.

[9]a) J. A. Grant, J.-M. Riethuisen, B. Moulaert, C. DeVos,

Ann. of Allergy, Asthma & Immunol. 2002, 88,

190-197; b) B. Zhou, Z.-F. Liu, G.-G. Deng, W. Chen,

M.-Y. Li, L.-J. Yang, Y. Li, X.-D. Yang, H.-B. Zhang,

Org. Biomol. Chem. 2016, 14, 9423-9430; c) N.

Plobeck, D. Delorme, Z.-Y. Wei, H. Yang, F. Zhou, P.

Schwarz, L. Gawell, H. Gagnon, B. Pelcman, R.

Schmidt, S. Y. Yue, C. Walpole, W. Brown, E. Zhou,

M. Labarre, K. Payza, S. St-Onge, A. Kamassah, P.-E.

Morin, D. Projean, J. Ducharme, E. Roberts, J. Med.

Chem. 2000, 43, 3878-3894; d) Y. Zhou, K. Duan, L.

Zhu, Z. Liu, C. Zhang, L. Yang, M. Li, H. Zhang, X.

Yang, Bioorg. Med. Chem. Lett. 2016, 26, 460-465. e)

X. Yang, B.-S. Kim, M. Li, P. J. Walsh, Org. Lett.

2016, 18, 2371-2374.

References

[1] C.-L. Sun, Z.-J. Shi, Chem. Rev. 2014, 114, 9219-9280.

[2] M. Yan, J. C. Lo, J. T. Edwards, P. S. Baran, J. Am.

Chem. Soc. 2016, 138, 12692-12714.

[3] a) N. A. Romero, D. A. Nicewicz, Chem. Rev. 2016,

116, 10075-10166; b) M. H. Shaw, J. Twilton, D. W. C.

MacMillan, J. Org. Chem. 2016, 81, 6898-6926; c) J. K.

Matsui, S. B. Lang, D. R. Heitz, G. A. Molander, ACS

Catalysis 2017, 7, 2563-2575.

[10] A. Studer, Chem. Eur. J. 2001, 7, 1159-1164.

[11] a) T. Kauffmann, A. Busch, K. Habersaat, E.

Käppelmonn, Angew. Chem. Int. Ed. 1973, 12,

569-570; b) T. Kauffmann, R. Eidenschink, Chem. Ber.

1977, 110, 651-655; c) T. Kauffmann, H. Berg, E.

Kiippelmann, D. Kuhlmann, Chem. Ber. 1977, 110,

2659-2664; d) T. Kauffmann, D. Berger, B. Scheerer,

A. Woltermann, Chem. Ber. 1977, 110, 3034-3039; e)

[4] a) I. Ghosh, T. Ghosh, J. I. Bardagi, B. König, Science

2014, 346, 725-728; b) K. L. Skubi, T. R. Blum, T. P.

Yoon, Chem. Rev. 2016, 116, 10035-10074; c) X. Lang,

J. Zhao, X. Chen, Chem. Soc. Rev. 2016, 45, 3026-3038.

[5] a) E. Doni, J. A. Murphy, Chem. Commun. 2014, 50,

6073-6087; b) J. A. Murphy, J. Org. Chem. 2014, 79,

14

10.1002/adsc.201800396

Advanced Synthesis & Catalysis

E. Erlenmeyer, J. Kunlin, Justus Liebigs Ann. Chem.

1899, 307, 163-170.

Manor, J. M. Anna, E. J. Schelter, J. Am. Chem. Soc.

2016, 138, 16266-16273; f) H. G. Roth, N. A. Romero,

D. A. Nicewicz, Synlett 2016, 27, 714-723.

[12] J. A. Fernandez-Salas, E. Marelli, S. P. Nolan, Chem.

Sci. 2015, 6, 4973-4977.

[18] a) C. Costentin, M. Robert, J.-M. Savéant, J. Am.

Chem. Soc. 2004, 126, 16051-16057; b) L. Pause, M.

Robert, J.-M. Savéant, J. Am. Chem. Soc. 1999, 121,

7158-7159; c) M. Kimura, H. Miyahara, N. Moritani, Y.

Sawaki, J. Org. Chem. 1990, 55, 3897-3902.

[13] H. Mohapatra, S. Umapathy, J. Phys. Chem. A 2009,

113, 6904-6909.

[19] K. Li, A. E. Weber, L. Tseng, S. J. Malcolmson, Org.

Lett. 2017, 19, 4239-4242.

[14] a)A. Claesson, C. Sahlberg, Tetrahedron 1982, 38,

363-368; b)R. R. Fraser, M. Bresse, N. Chuaqui-

Offermanns, K. N. Houk, N. G. Rondan, Can. J. Chem.

1983, 61, 2729-2734.

[20] Y. Koyama, P. G. Gudeangadi, Chem. Commun. 2017,

53, 3846-3849.

[15] a) J. Pancholi, D. J. Hodson, K. Jobe, G. A. Rutter, S.

M. Goldup, M. Watkinson, Chem. Sci. 2014, 5, 3528-

3535; b) T. D. Ashton, K. A. Jolliffe, F. M. Pfeffer,

Chem. Soc. Rev. 2015, 44, 4547-4595; c) G. Tu, Q.

Zhou, Y. Cheng, Y. Geng, L. Wang, D. Ma, X. Jing, F.

Wang, Synth. Met. 2005, 152, 233-236.

[21] Y. Goriya, H. Y. Kim, K. Oh, Org. Lett. 2016, 18,

5174-5177.

[22] C.-X. Guo, W.-Z. Zhang, H. Zhou, N. Zhang, X.-B.

Lu, Chem. Eur. J. 2016, 22, 17156-17159.

[23] D. Green, G. Patel, S. Elgendy, J. A. Baban, G.

Claeson, V. V. Kakkar, J. Deadman, Tetrahedron 1994,

50, 5099-5108.

[16] E. Kariv-Miller, Z. Vajtner, J. Org. Chem. 1985, 50,

1394-1399.

[17] a) S. R. Park, N. J. Findlay, J. Garnier, S. Zhou, M.

D. Spicer, J. A. Murphy, Tetrahedron 2009, 65,

10756-10761; b) I. Ghosh, L. Marzo, A. Das, R. Shaikh,

B. König, Acc. Chem. Res. 2016, 49, 1566-1577; c) Y.

Qu, H. Tateno, Y. Matsumura, T. Kashiwagi, M. Atobe,

Molecules 2017, 22, 413; d) M. Brasholz, Angew.

Chem. Int. Ed. 2017, 56, 10280-10281; e) H. Yin, Y.

Jin, J. E. Hertzog, K. C. Mullane, P. J. Carroll, B. C.

[24] A. E. Wendlandt, S. S. Stahl, Org. Lett. 2012, 14,

2850-2853.

15

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FULL PAPER

2-Azaallyl anions as light-tunable super-electron-

donors: coupling with aryl fluorides, chlorides, and

bromides

Adv. Synth. Catal. 2018, Volume, Page – Page

Qianmei Wang, Michal Poznik*, Minyan Li,

Patrick J. Walsh, Jason J. Chruma*

16

Article Doi

2-Azaallyl Anions as Light-Tunable Super-Electron-Donors: Coupling with Aryl Fluorides, Chlorides, and Bromides

DOI: 10.1002/adsc.201800396

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